valspodar

Valspodar is a non-immunosuppressive derivative of cyclosporin developed as a second-generation chemosensitizer to overcome multidrug resistance in cancer. Its primary mechanism is potent inhibition of the efflux transporter P-glycoprotein (ABCB1/MDR1), which is often overexpressed in tumor cells and mediates resistance by pumping chemotherapeutic agents out of cells. By inhibiting P-glycoprotein, valspodar restores intracellular concentrations and activity of various anticancer drugs in resistant tumors. It also inhibits other ABC transporters and can affect drug metabolism by inhibiting cytochrome P450-3A4 enzymes. Valspodar lacks the immunosuppressive and nephrotoxic properties seen with its parent compound cyclosporin A. It was studied for use in hematological malignancies (such as acute myeloid leukemia) and solid tumors but development was discontinued after disappointing results from phase III trials.

Brand names

Amdray

Other names

3'-keto-Bmt(1)-Val(2)-cyclosporin Acyclosporin D derivative